ALTERED EXPRESSIONS OF CARDIAC NA K-ATPASE ISOFORMS IN COPPER-DEFICIENT RATS/

Objective: The aim was to determine if copper deficiency affects the e xpression of Na/K-ATPase alpha isoforms in the rat heart. Methods: Cop per deficiency was induced by placing weanling rats on a copper defici ent diet for 4-5 weeks. Adult ventricular tissue, isolated ventricular myocytes, and brain stems of the control and deficient rats were comp ared for Cu, Zn-superoxide dismutase (CuZn-SOD) activity and for prote in and mRNA contents of Na/K-ATPase alpha isoforms. Results: In brain stem, where copper deficiency did not alter CuZn-SOD activity, mRNA an d protein levels of alpha isoforms also remained unchanged. In ventric ular tissue and ventricular myocytes, copper deficiency reduced CuZn-S OD activity, mRNAs of alpha(1), and alpha(2) isoforms, and the alpha(2 ) isoform protein. The alpha(1) isoform protein of ventricular tissue and its myocytes was marginally reduced by copper deficiency. Conclusi ons: In the rat ventricular tissue, oxidative stress resulting from co pper deficiency (1) enhances the turnover of the more oxidant sensitiv e alpha(2) isoform to a greater extent than the turnover of the alpha( 1) isoform; (2) regulates mRNA levels of alpha(1) and alpha(2) isoform s; and (3) contributes to the cardiomyopathy of copper deficiency.